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CONTEXT - Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.OBJECTIVE - The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function.DESIGN - This was a randomized, double-blind, placebo-controlled study.SETTING - This trial was conducted at Vanderbilt Clinical Research Center.PARTICIPANTS - Participants included overweight individuals with prediabetes.INTERVENTIONS - Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment.MAIN OUTCOME MEASURES - The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion.RESULT - Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation.CONCLUSIONS - Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.

This study aimed to provide data on the impact of known risk factors on endometrial cancer burden. Using data on 1199 endometrial cancer cases and 1212 frequency matched controls from a population-based case-control study carried out in urban Shanghai, China from 1997 to 2003, multivariable adjusted odds ratios were obtained from unconditional logistic regression analyses. Partial population-attributable risks were calculated and corresponding 95% confidence intervals were estimated using a bootstrap method. An estimated 16.94% of endometrial cancer cases were attributed to overweight or obesity; 8.39% to meat intake; 5.45% to nonregular tea drinking; 5.23% to physical inactivity; and 1.77% to family history of endometrial, breast, or colorectal cancers. Overall, these risk factors accounted for 36.01% (95% confidence interval: 28.55-43.11%) of total endometrial cancer cases. Similar results were observed when analysis was restricted to postmenopausal women. Among modifiable lifestyle factors, overweight and obesity accounted for the largest proportion of endometrial cancer in the study population. Lifestyle alterations, such as maintenance of healthy weight, regular exercise, consumption of less meat, and tea drinking, could potentially reduce endometrial cancer by more than one-third.

The main purpose of this study was to examine whether the Supplemental Nutrition Program for Women, Infants and Children (WIC) helped mothers of overweight/obese preschool children to cut down on dietary fat and sugar intake for their families. Data from the Children Eating Well for Health (CHEW) Nutrition Survey, a probability sample of 150 (50 each White, Black and Hispanic) families with preschoolers participating in the WIC program in Nashville/Davidson County, Tennessee, were analyzed using logistic regression modeling. Mothers who reported that the WIC program helped them reduce fat intake were 2.5 times more likely to have an overweight/obese child and 2.1 times more likely to be obese themselves. No significant effects were found for adding sugar. These results suggest that the mothers in this sample were applying WIC nutritional counseling to use food preparation techniques that cut down on added fats for themselves and their children who were at risk due to weight status.